Salient distractors delay visual search for less salient targets in additional-singleton tasks, even when the features of the stimuli are fixed across trials. According to the salience-driven selection hypothesis, this delay is due to an initial attentional deployment to the distractor. Recent event-related potential (ERP) studies found no evidence for salience-driven selection in fixed-feature search, but the methods employed were not optimized to isolate distractor ERP components such as the N2pc and distractor positivity (PD; indices of selection and suppression, respectively). Here, we isolated target and distractor ERPs in two fixed-feature search experiments. Participants searched for a shape singleton in the presence of a more-salient color singleton (Experiment 1) or for a color singleton in the presence of a less-salient shape singleton (Experiment 2). The salient distractor did not elicit an N2pc, but it did elicit a PD on fast-response trials. Furthermore, distractors had no effect on the timing of the target N2pc. These results indicate that (a) the distractor was prevented from engaging the attentional mechanism associated with N2pc, (b) the distractor did not interrupt the deployment of attention to the target, and (c) competition for attention can be resolved by suppressing locations of irrelevant items on a salience-based priority map.

Report of a second target (T2) is impaired when presented within 500 ms of the first (T1). This attentional blink (AB) is known to cause a delay in T2 processing during which T2 must be stored in a labile memory buffer. We explored the buffer's characteristics using different types of masks after T2. These characteristics were inferred by determining what attributes of T2 are hindered by a given form of masking. In Experiments 1–3, trailing metacontrast and four-dot masks produced ABs of equal magnitudes, implicating the onset-transient triggered by the mask as the mechanism underlying the AB and strongly suggesting a locus in early vision. In Experiment 4, metacontrast and four-dot masks were presented in a common-onset masking (COM) paradigm in which a brief, combined display of T2 and the mask was followed by a longer display of the mask alone. COM is thought to occur late in the sequence of processing events. No AB occurred with COM, confirming the critical role of the mask's onset transients and ruling out a high-level locus for the labile memory buffer.

The presence of a salient distractor interferes with visual search. According to the salience-driven selection hypothesis, this interference is because of an initial deployment of attention to the distractor. Three event-related potential (ERP) findings have been regarded as evidence for this hypothesis: (a) salient distractors were found to elicit an ERP component called N2pc, which reflects attentional selection; (b) with target and distractor on opposite sides, a distractor N2pc was reported to precede the target N2pc (N2pc flip); (c) the distractor N2pc on slow-response trials was reported to occur particularly early, suggesting that the fastest shifts of attention were driven by salience. This evidence is equivocal, however, because the ERPs were noisy (b, c) and were averaged across all trials, thereby making it difficult to know whether attention was deployed directly to the target on some trials (a, b). We reevaluated this evidence using a larger sample size to reduce noise and by analyzing ERPs separately for fast- and slow-response trials. On fast-response trials, the distractor elicited a contralateral positivity (PD)—an index of attentional suppression—instead of an N2pc. There was no N2pc flip or early distractor N2pc. As it stands, then, there is no ERP evidence for the salience-driven selection hypothesis.

Recent demonstrations of the anticonvulsant properties of agmatine suggest it may be considered as a potential adjunct for protection against seizure. We investigated the possibility of an additive anticonvulsant effect between low doses of agmatine and morphine. The thresholds for the clonic seizures induced by the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist, pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1-3mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threshold. Pretreatment with a per se non-effective dose of agmatine (1mg/kg) potentiated the anticonvulsant effect of morphine. The combination of subeffective doses of agmatine and morphine led to potent anticonvulsant effects. The pro-convulsant effect of morphine was attenuated by agmatine. Yohimbine with a dose (1mg/kg) incapable of affecting seizure threshold reversed the effect of agmatine on both anticonvulsant and pro-convulsant effects of morphine. These results suggest that agmatine potentiates the anticonvulsant effect of morphine and alpha 2-adrenoceptors may be involved in this effect.

This study was conducted to evaluate the effect of simvastatin (40 mg/day) as an adjuvant therapy to interferon beta (IFNb 1a, 30 microg once weekly) in relapsing-remitting multiple sclerosis patients, compared with placebo.

There is an increasing body of evidence that the central nervous system is affected by cholestatic liver disorders. Cholestasis has been shown to result in a decreased seizure propensity which is believed to be mediated by an increased opioidergic tone and nitric oxide (NO) signaling pathway. In this study, we used a reversible chemically-induced cholestasis model in mice to investigate the changes in seizure susceptibility. The cholestasis was induced by intragastric administration of alpha-naphthylisothiocyanate (ANIT) (100 mg/kg) or vehicle (corn oil). The threshold to generalized clonic seizures induced by timed intravenous infusion of pentylenetetrazole (PTZ) was used as an index of seizure propensity. The role of opioid receptors and NO pathway in the changes of seizure threshold, and the responsiveness to the anticonvulsant effect of opioid agonist, morphine, during and after the resolution of cholestasis was studied in this reversible paradigm of cholestatic disease. A significant increase in cholestasis-related biochemical markers as well as in clonic seizure threshold was observed; it was maximal at day 3 after cholestasis induction and slowly decreased to normal thereafter. Seizure threshold rise was inhibited by chronic administration of the opioid antagonist naltrexone or acute administration of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO production. Co-administration of subeffective doses of L-NAME and naltrexone showed an additive effect. Injection of an anticonvulsant dose of morphine on day 7 after cholestasis induction did not increase seizure threshold, suggestive of a downregulation of receptors even after cholestasis resolution. These data shows that ANIT-induced cholestasis leads to a reversible increased resistance to PTZ-induced seizures through an opioid/NO-mediated pathway, and is probably accompanied by downregulation of opioid receptors.

Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). T1-based theories ascribe this attentional blink (AB) to a T1-initiated period of inattention. Distractor-based theories ascribe it to a disruption of input control caused by post-T1 distractors. The finding that an AB occurs without intertarget distractors (Nieuwenstein, Potter, & Theeuwes, Journal of Experimental Psychology: Human Perception and Performance 35:159-169, 2009) seemingly disconfirms distractor-based theories. The present experiments addressed different ways in which distractor-based theories might account for that finding. Intertarget events were varied in four experiments. Experiment 1 replicated Nieuwenstein, Potter, and Theeuwes's findings. The next two experiments tested two ways (lack of visual stimulation, violation of expectation) in which the blank intertarget interval might cause an AB. Experiment 4 explored whether backward-masking of T1 can account entirely for the larger AB obtained with intervening distractors or whether distractors also disrupt input control. The results disconfirm predictions from distractor-based theories and support the claim of T1-based theories that T1 processing alone is sufficient for the AB. Simulations based on the eSTST (Wyble, Bowman, & Nieuwenstein, Journal of Experimental Psychology: Human Perception and Performance 35:787-807, 2009) and the B&B models (Olivers & Meeter, Psychological Research, 115, 836-863 2008) were compared. Predictions were more accurate from the T1-based theory (eSTST) than from the distractor-based theory (B&B).

Background: Transcranial magnetic stimulation (TMS) can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD) increases, it is critical to understand their reproducibility (i.e., test–retest reliability) in the populations of interest.

Objective: Reproducibility of TMS measures was evaluated in older adults, including healthy, AD, and Type-2 diabetes mellitus (T2DM) groups.

Methods: Participants received two identical neurophysiological assessments within a year including motor thresholds, baseline motor evoked potentials (MEPs), short- and long-interval intracortical inhibition (SICI, LICI) and intracortical facilitation (ICF), and MEP changes following intermittent theta-burst stimulation (iTBS). Cronbach’s α coefficients were calculated to assess reproducibility. Multiple linear regression analyses were used to investigate factors related to intraindividual variability.

Results: Reproducibility was highest for motor thresholds, followed by baseline MEPs, SICI and LICI, and was lowest for ICF and iTBS aftereffects. The AD group tended to show higher reproducibility than T2DM or controls. Intraindividual variability of baseline MEPs was related to age and variability of RMT, while the intraindividual variability in post-iTBS measures was related to baseline MEP variability, intervisit duration, and Brain-derived neurotrophic factor (BDNF) polymorphism.

Conclusion: Increased reproducibility in AD may reflect pathophysiological declines in the efficacy of neuroplastic mechanisms. Reproducibility of iTBS aftereffects can be improved by keeping baseline MEPs consistent, controlling for BDNF genotype, and waiting at least a week between visits.

Significance: These findings provide the first direct assessment of reproducibility of TMS measures in older clinical populations. Reproducibility coefficients may be used to adjust effect- and sample size calculations for future studies.

Relative blindsight is said to occur when different levels of subjective awareness are obtained at equality of objective performance. Using metacontrast masking, Lau and Passingham (2006) reported relative blindsight in normal observers at the shorter of two stimulus-onset asynchronies (SOAs) between target and mask. Experiment 1 replicated the critical asymmetry in subjective awareness at equality of objective performance. We argue that this asymmetry cannot be regarded as evidence for relative blindsight because the observers’ responses were based on different attributes of the stimuli (criterion contents) at the two SOAs. With an invariant criterion content (Experiment 2), there was no asymmetry in subjective awareness across the two SOAs even though objective performance was the same. Experiment 3 examined the effect of criterion level on estimates of relative blindsight. Collectively, the present results question whether metacontrast masking is a suitable paradigm for establishing relative blindsight. Implications for theories of consciousness are discussed.